Multiscale conformational heterogeneity in staphylococcal protein a: possible determinant of functional plasticity.

Published

Journal Article

The Staphylococcus aureus virulence factor staphylococcal protein A (SpA) is a major contributor to bacterial evasion of the host immune system, through high-affinity binding to host proteins such as antibodies. SpA includes five small three-helix-bundle domains (E-D-A-B-C) separated by conserved flexible linkers. Prior attempts to crystallize individual domains in the absence of a binding partner have apparently been unsuccessful. There have also been no previous structures of tandem domains. Here we report the high-resolution crystal structures of a single C domain, and of two B domains connected by the conserved linker. Both structures exhibit extensive multiscale conformational heterogeneity, which required novel modeling protocols. Comparison of domain structures shows that helix1 orientation is especially heterogeneous, coordinated with changes in side chain conformational networks and contacting protein interfaces. This represents the kind of structural plasticity that could enable SpA to bind multiple partners.

Full Text

Duke Authors

Cited Authors

  • Deis, LN; Pemble, CW; Qi, Y; Hagarman, A; Richardson, DC; Richardson, JS; Oas, TG

Published Date

  • October 7, 2014

Published In

Volume / Issue

  • 22 / 10

Start / End Page

  • 1467 - 1477

PubMed ID

  • 25295398

Pubmed Central ID

  • 25295398

Electronic International Standard Serial Number (EISSN)

  • 1878-4186

Digital Object Identifier (DOI)

  • 10.1016/j.str.2014.08.014

Language

  • eng

Conference Location

  • United States